1. Field of the Invention
This invention relates to a contrast mechanism referred to as extinction contrast which can be used for a variety of x-ray imaging applications. The method and system of this invention relates to an x-ray imaging modality that uses an analyzer crystal after the object. The imaging contrast of this invention is based on attenuation and refraction.
2. Description of Related Art
One type of diffraction enhanced imaging (DEI) is described in Chapman et al., U.S. Pat. No. 5,987,095.
Articular cartilage covers the ends of bones in synovial joints and provides elasticity, distribution of load, resistance to compressive forces, smooth articulation and cushioning of the subchondral bone during joint movements. Tissue is composed of collagen, primarily type II collagen, entrapping compressed proteoglycan aggregates.
The degeneration of articular cartilage is a component of pathological processes that result in the destruction of the tissue and leads to the deformation of the entire joint. This serious condition, known as osteoarthritis, includes a number of related, overlapping osteoarthritic disorders that are among the leading causes of immobilization within our society and affects probably 85% of elderly people. Use-related joint pain is one of the first signs of disease; however, pain is not always an early warning sign. By the time pain becomes a symptom, successful conservative treatments that could lead to regeneration of the tissue are too late. Presently, several operative methods, including total joint replacement, exist for some but not all the joints. Conventional procedures for repairing of transplanting articular cartilage do not restore a normal articular surface.
Techniques have been applied to access the health or disease of articular cartilage based on x-ray, ultrasound or nuclear magnetic resonance. Among these techniques, conventional radiography has the highest resolution and is the first and most frequently used imaging method to detect joint abnormalities. Conventional radiographs allow the evaluation of articular cartilage only indirectly through the measurement of the height of the joint space, the distance between the corresponding bone surfaces within a joint. Consequently, conventional radiography is sensitive only in cases of advanced disease. Focal cartilage defects or structural abnormalities in early stages of the degenerative process are generally not visible in radiographs.
Conventional x-ray radiography relies on x-ray absorption differences between regions of the object to provide image contrast. Cartilage tissue has little x-ray absorption contrast because the x-ray absorption is similar to soft tissue and synovial fluid. Therefore cartilage cannot be easily seen in conventional radiograph. Diffraction Enhanced Imaging (DEI) is a x-ray radiographic technique that derives contrast from x-ray refraction and scatter rejection (extinction) in addition to the absorption of conventional radiography. These two new contrast sources can in some cases allow visualization of features that are not possible using conventional methods. Certain of DEI are described in U.S. Pat. No. 5,987,095, the entire disclosure of which is incorporated into the specification by reference. The method of this invention uses highly collimated x-rays prepared by x-ray diffraction from perfect single-crystal silicon. These collimated x-rays are of single x-ray energy, practically monochromatic, and are used as the beam to image an object. A schematic of the DEI setup used at the synchrotron is shown in FIG. 1. In this case, the collimated x-rays are prepared by the two crystal sets identified as the Si (3,3,3) monochromator. Once this beam passes through the object, another crystal of the same orientation and using the same reflection is introduced. This crystal is called the analyzer. If this crystal is rotated about an axis perpendicular to the plane shown in FIG. 1, the crystal will rotate through the Bragg condition for diffraction and the diffracted intensity will trace out a profile that is called the rocking curve. The profile will be roughly triangular and will have peak intensity close to that of the beam intensity striking the analyzer crystal. The width of the profile is typically a few microradians wide (3.6 microradians within a full width of half maximum (FWHM) at 18 keV using the Si (3,3,3) reflection). The character of the images obtained change depending on the setting of the analyzer crystal. To extract refraction information, the analyzer is typically set to the half intensity points on the low and high angle sides of the rocking curve. For optimal scatter rejection sensitivity, the analyzer is typically set to the peak of the rocking curve. To image the rejected scatter, the analyzer is set in the wings of the rocking curve.
The DEI method and system of this invention have been applied to image human articular cartilage from the distal part (talas) of the ankle (talocrural) joint that are eight macroscopically normal or display damages typical of early degenerative stages. A human ankle joint indicating the position of the talus within a foot skeleton is shown in FIG. 2.
The tali were obtained within 24 hours of death through the Regional Organ Bank of Illinois with institutional approval. None of the 12 donors used in this study has a known history of osteoarthritic disease. All tali were fixed in 4% paraformaldehyde. For the normal ankles (n=4), the ages were 34 to 54 years, and for the damaged ankles (n=8) that ages were 51 to 66 years. All experiments were performed at the X15A beamline at the National Synchrotron Light Source, Brookhaven National Laboratory, Upton, N.Y. The tali were x-rayed in a posterior to anterior direction.
Examples of a normal and several damaged tali with corresponding DEI according to this invention are shown in FIGS. 3, 4 and 5. The cartilage tissue is clearly detected and distinguished from bone. These images were acquired at an 18 keV x-ray photon energy. The structure of cartilage on the normal talus looks homogeneous, with an average height of 1.5 mm and moderate density ( FIG. 4 and FIG. 6 at 18 keV and FIG. 10 at 30 keV). This pattern changes in damaged cartilage, the tissue is no longer homogeneous but shows patterns that suggest structural alterations (FIGS. 7, 8, 9 at 18 keV and FIGS. 11, 12, 13 at 30 keV) and that correspond with the sites of macroscopic damage (compare with photographs in FIGS. 15, 16, 17).
At higher magnification of certain areas, distinct structural alterations are visible. Of special interest are the thin white lines on a dark background (arrows shown in FIGS. 11-17). It is possible that the white lines represent certain structural changes which give rise to specific refraction patterns, extinction effects and/or absorption contrasts detected by the DEI imaging system according to this invention, which would most likely develop at the edges of cartilage fibrillations, fissures or defects. However, condensed collagen fibrils may also cause such effects. The contrast may further be enhanced because the normally entrapped large proteoglycans are lost due to the damage of the collagen network and therefore the absorption of the x-ray beam is different in this area.
An example of how the character of a subject image changes depending on the setting of the analyzer crystal can be seen in FIG. 18. This is a rocking curve with the corresponding images of the talar dome at various analyzer crystal angles and at the 30 keV energy level. Note the change in appearance of the contrast heterogeneities observed in the images throughout the rocking curve. In the subsequent data sets, images were obtained from at or near the top of the rocking curve (unless specified otherwise) and at either 18 keV or 30 keV, as specified.
As used in the claims and throughout this specification the phrase xe2x80x9cat or near the peak of the rocking curve anglexe2x80x9d is intended to relate to at 18 keV using the silicon (3, 3, 3) reflection within xc2x1 about 1.0 to about 1.8 microradians of the angle of the crystal analyzer. Changing the energy level or changing the reflection will alter the range of microradians of the angle of the crystal analyzer, as would be apparent to a person skilled in the art of diffraction physics of crystals.
The diffraction enhanced (DE) image of a portion of an osteoarthritic knee removed in the course of total knee replacement is shown in FIG. 19. At this stage, only small areas of the joint surface are still covered with an intensely modified cartilage. Specifically, the DE image (FIG. 19) depicts a small 3 cm wide segment of such residual cartilage on top of the femoral bone. Major horizontal heterogeneities in contrast are visible. Further analysis is required to determine the nature of these contrasts as condensed/collapsed collagen fiber networks or perhaps a reflection of another unknown molecular feature within the tissue. The regular radiographic image of the same area does not show the cartilage or these features (FIG. 20).
Preliminarily, the contrast heterogeneity features observed below the cartilage surface in the DE images in some of the specimens have been histologically validated. FIG. 21 shows a section of talar dome as it is grossly observed (FIG. 21) and in its DE image at 18 keV (FIG. 22) and at 30 keV (FIG. 23). A normal-looking region of the specimen as depicted in square number 1 can be seen in its Safranin O/fast green histological preparation in FIG. 24. Under polarized light, the same specimen displays a normal pattern of birefringence in the superficial and deep zones (FIG. 25). A region of the talar dome displaying a xe2x80x9cbubbledxe2x80x9d region of cartilage (xe2x80x9cchondrophytexe2x80x9d) in which contrast heterogeneities (dark spots) can be seen is depicted in square number 2. FIG. 26 is the Safranin O/fast green histological preparation of the chondrophyte region. The dark spot observed in the DE image in square number 2 appears, histologically, to be a vacuolated space (e.g. blister) in the cartilage surrounded by cartilage in a state of degeneration/remodeling. The polarized microscopic section of the same region (FIG. 27) shows that the collagen fibers surrounding the xe2x80x9cvacuolationxe2x80x9d have lost their normal birefringent pattern and thus display disorganization. It is apparent that the DE images reflect the general status of cartilage normality or degeneration in these specimens.
Although DEI is in its infancy in terms of development, an assessment of the potential of DEI for practical applicability in intact joints is warranted at this time. The DE images of the intact knee joint with all of its surrounding soft tissues, except skin, can be seen in FIGS. 28 and 29. FIG. 28 was taken at or near the top of the rocking curve and FIG. 29 was taken at xe2x88x923.6 microradians. These are an image of the medial femoral and tibial condyles with their associated articular hyaline cartilage and fibrocartilaginous menisci. The arrows point to the boundaries of the articular hyaline cartilage surfaces. Both the articular cartilage and menisci can be delineated even through the surrounding tissues.
It is possible to image animal articular cartilage with DEI. FIG. 30 shows cartilage and bone of the femoral condyle of a New Zealand white rabbit. FIG. 31 is a DE image of the intact knee joint showing joint tissues including the articular cartilage of the femoral condyles. This is quite remarkable considering that the cartilage is only approximately 110xcexc thick. It is also noteworthy that the articular cartilage can be seen even through the surrounding soft tissues, including skin and hair. FIG. 32 shows the DE image of a disarticulated femur taken from a rabbit knee joint that had been injected with the cartilage matrix damaging enzyme, chymopapain, three weeks prior to the animal sacrifice. Small areas of, what appears to be, damage (in the form of refraction/extinction features) correspond to damage on the right femoral condyle as depicted histologically (see the arrow in FIG. 32).
Application of the DEI method and system of this invention, particularly as it applies shows improved contrast of specific structures within the human breast tissue in a clinical setup. The DEI method and system of this invention can extend skeletal radiology, in addition to its use for imaging of cartilage. X-rays are ideal to evaluate changes in the subchondral bone which are a major component of osteoarthritic disorders.
Standard radiographic evaluation of osteoarthritic disorders involves detecting the narrowing that occurs in a joint space as a joint cartilage is destroyed during a disease process only because that cartilage tissue is invisible in x-ray imaging. A high resolution image of human articular cartilage from the talar dome of an ankle joint, for example, can now be obtained using Diffraction Enhanced Imaging (DEI), an x-ray radiographic technique that has contrast from x-ray refraction, scatter rejection and absorption. Defects, structural abnormalities, and loss of articular cartilage can be detected in the tissue using the DEI method and system according to this invention. DEI can provide information about an internal structure of cartilage before other visual evidence of disease has evolved.
The DEI method and system of this invention can be used to explore the application of high intensity and inherent vertical collimation of synchrotron radiation to the creation of a monoenergetic line scan system for radiography of thick absorbing objects. A x-ray analyzer crystal can be used as a scatter rejection optic to diffract a beam that is transmitted through an imaged object. With this scatter rejection optic the system of this invention may be sensitive to refractive index effects within the imaged object and the x-ray absorption and scattering by the object. The setting of the analyzer at or near the top of the rocking curve, places the analyzer at a setting that rejects those rays that are scattered or refracted. The result is to develop image contrast from the structures that create this effect. Cartilage is a tissue of this type of structure.
Images taken with an analyzer and normal radiographs of objects show that the rejection of scatter can be a major source of contrast with the DEI imaging geometry. With the DEI imaging method and system of this invention, additional contrast can be many times the normal absorption contrast of an object. To account for additional source of image contrast in DEI images, the term apparent absorption is used and relates to the combined absorption and extinction processes. Extinction relates to the loss of intensity due to scattering that occurs as the beam traverses the object and this type of extinction is commonly identified as secondary extinction. Use of the term extinction in this invention is slightly different from use in optics where the term extinction includes absorption and scattering power loss. The power loss from the direct beam due to scattering is referred to as extinction.
Sources of the enhanced image contrast explain why increased contrast is a result of extinction effects, which provides opportunity for imaging based on these properties. Because the contrast of an image based on extinction can be much higher than contrast based on x-ray attenuation, it is possible to detect smaller inhomogeneities, such as tumors in medical images or micro-fractures in industrial parts.
Monochromator and analyzer system capabilities to resolve refraction effects depend on the imaging energy as 1/energy. The scattering properties of various elements are energy dependent as 1/energy2 which will allow optimization of imaging system energy to maximize contrast due to extinction while maintaining refraction contrast. Thus, the modality may be optimally applied at higher x-ray energies, which provides better penetration in non-destructive testing and/or lower doses in medical imaging.
It is known to apply diffractive optics to imaging problems for observing refraction and ultra-small angle scattering contrast effects. The results quantify the role of ultra-small angle scattering and the scatter rejection in the DEI method and system of this invention. Also, imaging experiments based on imaging the scatter from objects, for example scatter imaging references, are known. This known technique relies on imaging a direct beam that is mostly devoid of scatter and is complementary to scatter imaging. There is an interest in phase contrast imaging that uses high transverse coherence of small source points, such as that of third-generation synchrotron sources. Phase contrast images are limited to either thin objects or high x-ray imaging energies. The DEI method and system of this invention is similar to phase contrast imaging due to sensitivity to refraction. However, the additional benefit of the analyzer crystal in this invention allows refraction determination in highly absorbing objects and produces additional contrast due to its scatter rejection capabilities.
With the DEI imaging according to this invention, it is possible to visualize articular cartilage using the new x-ray modality, referred to as DEI. Moreover, the combination of the high spatial resolution that can be achieved with x-rays, and the independent detection of refraction patterns, scatter rejection and x-ray absorption make the method of the invention capable of detecting not only articular cartilage and gross cartilage defects but also structural abnormalities within the tissue. With the DEI imaging of this invention, it is possible to detect cartilage degeneration even in early stages, such as before any clinical evidence of disease evolves. The DEI imaging of this invention can be used as a part of a new x-ray generation in research as well as in clinical radiology, especially in skeletal x-ray, and in other areas where soft tissue contrast needs to be enhanced.